From the simple to the complex – supramolecular interactions in pharmaceutical materials

From the simple to the complex – supramolecular interactions in pharmaceutical materials

Approximately two thirds of all marketed medicines are solid, e.g. tablets or capsules, with the active drug being in the solid state as well. Like other small organic molecules, drug compounds can show crystal polymorphism, i.e. the ability to crystallise in different molecular arrangements. In addition, solvent of crystallisation can be incorporated. Due to their altered physico-chemical characteristics, unexpected or undetected appearance of these different materials may pose a severe risk to the safety and efficiency of any medicine, a fact that has led to major recalls of already marketed medicines.
In this talk I will present our work in the field of pharmaceutical solid-state and pre-formulation research. Starting from the current state-of-the-art crystal form screening, the gathered information and knowledge of the physicochemical characteristics of the found crystal forms give a good understanding of how a particular compound will behave under formulation conditions, during storage, as well as when applied by the patient. However, very little translation can be done to another compound treating the same disease state, which will potentially differ significantly in its chemical structure. I will thus move to more complex approaches to understand the underlying physical phenomena leading to a particular crystal form. Using results from neutron scattering and NMR techniques, in addition to a multitude of solid-state characterisation techniques, I will showcase what can be learned from the supramolecular interactions within the crystals with respect to their stability and their formation during crystallisation. I will specifically focus on crystal hydrates incorporating water, the potentially most difficult materials for pharmaceutical formulation due to their inherent low water-solubility.